Nozaki M, Akera T, Lee C Y, Brody T M
J Pharmacol Exp Ther. 1975 Mar;192(3):506-12.
Changes in growth rate and the development of tolerance and physical dependence during repeated morphine administration were compared in different age groups of rats. Chronic treatment of rats for 3 weeks with increasing doses of morphine resulted in an inhibition of the growth rate of older rats but not of younger rats. The magnitude and time course of the loss of body weight upon morphine withdrawal in morphine-treated rats were independent of the age of the animal. Morphine increased the "pain" threshold in rats as monitored by the electric foot-shock technique. These analgesic effects were greater in 12-week-old rats than in 4- or 7-week-old rats. Repeated administration of morphine resulted in a gradual loss of the analgesic response to morphine in all age groups. However, the rate of development of tolerance to morphine was faster in younger rats than in older rats when these animals were injected repeatedly either with a fixed dose or with equipotent doses of morphine. These investigations indicate that the rate of the development of tolerance to morphine is significantly affected by the age of the subject.
在不同年龄组的大鼠中比较了重复给予吗啡期间生长速率的变化以及耐受性和身体依赖性的发展情况。用递增剂量的吗啡对大鼠进行3周的慢性治疗导致老年大鼠的生长速率受到抑制，但年轻大鼠未受影响。吗啡处理的大鼠在撤药时体重减轻的幅度和时间进程与动物年龄无关。通过电足电击技术监测发现，吗啡提高了大鼠的“疼痛”阈值。这些镇痛作用在12周龄的大鼠中比在4周龄或7周龄的大鼠中更强。重复给予吗啡导致所有年龄组对吗啡的镇痛反应逐渐丧失。然而，当用固定剂量或等效剂量的吗啡反复注射这些动物时，年轻大鼠对吗啡耐受性的发展速度比老年大鼠更快。这些研究表明，吗啡耐受性的发展速度受实验对象年龄的显著影响。
